1. Field of the Invention
The present invention relates to a novel anthracycline glycoside derivatives of the following formula (I): ##STR2## wherein R.sub.1 and R.sub.2 represent hydrogen atom, respectivelly, or include both straight or branch chain alkylidene group of 1-10 carbon atoms; R.sub.3 represents hydrogen atom, straight or branch chain alkyl group of 1-10 carbon atoms, straight or branch chain alkyl-oxycarbonyl group of 1-10 carbon atoms or 3-membered to 6-membered heterocycle containing one nitrogen atom with adjacent alkylene group such as pyrrolidine and N-(t-butoxycarbonyl-pyrrolidine; R.sub.4 and R.sub.5 represent hydrogen atom or alkyl group of 1-5 carbon atoms, respectively; and n represents 0 or an integer of 1-10, or pharmaceutically acceptable salt thereof.
2. Description of the Prior Art
As the antibiotics of anthracycline series, daunorubicin disclosed in U.S. Pat. No. 3,997,662 and doxorubicin disclosed in U.S. Pat. No. 3,590,028 were obtained from the fermented broth of Actinomyces species. The anthracyclines have a broad spectrum antitumor activity and have been used as chemotherapeutics against malignant tumors.
The formula (A) of the above anthracyclines is as follows: ##STR3## wherein R represents hydrogen atom or hydroxyl group.
In addition, the formula (B) of 2-fluoro-substituted anthracycline derivative disclosed in Japanese Patent Laid Open Publication No. Sho 62-145,097 is as follows: ##STR4## wherein R represents hydrogen atom or hydroxyl group.
Moreover, the formula (C) of a soluble derivative of the above-identified compound (B) disclosed in Japanese Patent Laid Open Publication No. Sho 63-141,992 is as follows: ##STR5## wherein R represents --(CH.sub.2).sub.m H (m represents 0 or an integer of 1 to 6) or --(CH.sub.2).sub.n COOH (n represents 0 or an integer of 1 to 10).
However, since the above-identified anthracyclines exhibit certain undesirable side effects, they have had a limited usefulness of anthracyclines such as daunorubicin and doxorubicin derivatives. One of their more serious side effects is their cardiotoxicity which severely restricts the dosages and the frequency with which they can be administered and in turn, limits their overall effectiveness as a chemotherapeutic agent against malignant tumors. And one of the other disadvantages of the above known compounds is that they have relatively low solubility in water. In view of the low water solubility, these compounds are difficult to administer in amounts which would be effective in the treatment of some cancers.